Bis-styrylpyridine and bis-styrylbenzene derivatives as inhibitors for Abeta fibril formation

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1466-70. doi: 10.1016/j.bmcl.2006.10.090. Epub 2006 Nov 2.

Abstract

New bis-styrylpyridine and bis-styrylbenzene derivatives were designed and synthesized. These 34 compounds were evaluated by Abeta fibril formation inhibitory assay using thioflavin T as a dye (named ThT assay). Most of them showed excellent inhibitory activities for Abeta fibril formation at IC50 of 0.1-2.7 microM which is comparable to curcumin (IC50 of 0.8 microM). Among them, nine compounds were screened for their cytotoxicities on HT-22 cell by MTT assay at 1, 10, and 50 microM. In particular, I-7 and II-2 exhibited the best combination of inhibitory activity and compound cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Animals
  • Benzene Derivatives / chemical synthesis*
  • Benzene Derivatives / pharmacology*
  • Benzothiazoles
  • Cell Line
  • Cell Survival / drug effects
  • Drug Design
  • Inhibitory Concentration 50
  • Mice
  • Pyridines / chemical synthesis
  • Pyridines / pharmacology
  • Structure-Activity Relationship
  • Styrenes / chemical synthesis
  • Styrenes / pharmacology
  • Thiazoles

Substances

  • Amyloid beta-Peptides
  • Benzene Derivatives
  • Benzothiazoles
  • Pyridines
  • Styrenes
  • Thiazoles
  • thioflavin T